This invention relates to a new process for making certain antiinflammatory 3-[hydroxy-2-(aryl)methylene]-2-oxo-1H-indole-1-carboxamides. More particularly, it relates to production of said compounds by reductive debromination or deiodination of 3-(bromo- and/or iodo-substituted)aroyl-2-oxindole-1-carboxamides.
Prior to this invention, 3-[hydroxy-2-(aryl)methylene]-2-oxo-1H-indole-1-carboxamides have been prepared according to one of the routes indicated below in sequence A: ##STR1##
In the above reaction sequences, each of variables X, Y, R.sup.1 and R.sup.2 represents a wide range of substituents. Representative values of X are hydrogen, alkyl, cycloalkyl, alkoxy, alkylthio, trifluoromethyl, alkylsulfinyl, alkylsulfonyl, alkanoyl, benzoyl, thenyl, halo and alkanamido; of Y are hydrogen, halo, alkyl, alkoxy, cycloalkyl and trifluoromethyl. Representative values of R.sup.1 are alkyl, cycloalkyl, cycloalkenyl, phenyl, substituted phenyl, phenylalkyl; (substituted phenyl)alkyl, phenoxyalkyl, (substituted phenoxy)alkyl, (thiophenoxy)alkyl, (thiophenoxy)alkyl, alkyl, naphthyl, bicyclo[2.2.1]heptan-2-yl, bicyclo[2.2.1]hept-5-en-2-yl and --(CH.sub.2).sub.n --Q--R.sup.o ; wherein n is zero, 1 or 2; Q is a divalent radical derived from furan, thiophene, pyrrole, pyrazole, imidazole, thiazole, isothiazole, oxazole, isoxazole, 1,2,3-thiadiazole, 1,3,4-thiadiazole, 1,2,5-thiadiazole, tetrahydrofuran, tetrahydrothiophene, tetrahydropyran, tetrahydrothiopyran, pyridine, pyrimidine, pyrazine, benzo[b]furan and benzo[b]thiophene; and R.sup.o is hydrogen or alkyl, and of R.sup.2 are hydrogen, alkyl, cycloalkyl, benzyl, furyl, thienyl, pyridyl, phenyl and substituted phenyl.
Discussions of both routes are presented in U.S. Pat. No. 4,556,672, issued Dec. 3, 1985. Substituent R.sup.1 --CO-- is attached to the oxindole nucleus by reacting the appropriate 2-oxindole or 2-oxindole-1-carboxamide with an activated derivative of acid R.sup.1 COOH. The activated derivative can be an acid halide, symmetrical acid anhydrides, mixed acid anhydrides mixed carboxylic-carbonic anhydrides, carboxylic acids and acyl imidazoles.